β,β-Dimethylacrylalkannin

β,β-Dimethylacrylalkannin (Arnebin 1) is an orally active FGFR1 inhibitor (IC₅₀=2.5 μM) and the main active component of Lithospermum erythrorhizon. β,β-Dimethylacrylalkannin blocks downstream signaling by binding to the ATP pocket of FGFR1, and regulates the CDK1/Cdc25C pathway and ROS-JNK axis, thereby inducing G2/M phase arrest, necrosis and apoptosis in cancer cells, and inhibiting tumor proliferation. β,β-Dimethylacrylalkannin also acts as a colistin adjuvant to disrupt the cell membrane of Gram-negative bacteria. β,β-Dimethylacrylalkannin exhibits significant tumor-inhibitory effects with no obvious toxicity in PDX models, but chronic exposure to high doses may alter the relative lung/liver weights of rats, while acute exposure to high doses causes responses such as reduced motor activity. β,β-Dimethylacrylalkannin finds wide application in studies related to hepatocellular carcinoma, colorectal cancer, colistin-resistant bacterial infections, hepatitis and psoriasis^[1][2][3][4]. In Vitro:β,β-Dimethylacrylalkannin (0.1-100 μM; 24, 48 h) significantly reduces the viability of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells in a dose-dependent manner^[1].
β,β-Dimethylacrylalkannin (1-5 μM; 24 h) regulates cell cycle regulatory proteins in HepG2 and Huh7 hepatocellular carcinoma cells, reduces the activity of the Cyclin B1/CDK1 complex, and inhibits Cdc25C function, thereby inducing G2/M phase arrest^[1].
β,β-Dimethylacrylalkannin (30 μM; 8-24 h) induces necrosis in HepG2 and Huh7 hepatocellular carcinoma (HCC) cells, and this effect is not inhibited by ferroptosis or necroptosis inhibitors^[1].
β,β-Dimethylacrylalkannin (2.5 μM; 72 h) inhibits the growth of patient-derived colorectal cancer organoids, such as Huh7 organoids^[1][2].
β,β-Dimethylacrylalkannin (5-10 μM; 24 h) induces G1-phase cell cycle arrest in HCT 116, DLD-1, SW 620 and HCT-15 colorectal cancer cells^[2].
β,β-Dimethylacrylalkannin inhibits FGFR1-mediated downstream signaling pathways in HCT 116, DLD-1, SW 620 and HCT-15 colorectal cancer cells, and reduces the phosphorylation levels of FRS2, JAK2, STAT3 and MEK1/2 without altering the total protein levels^[2].
Combination treatment with β,β-Dimethylacrylalkannin (8 μg/mL; 1 h) and polymyxin alters the gene expression profiles of polymyxin-resistant *Escherichia coli* BW25113-mcr-1 and *Escherichia coli* BW25113-pmrBR93P, significantly downregulating *lptD* and upregulating *marR*, thereby disrupting LPS transport and efflux pump activity^[3]. In Vivo:β,β-Dimethylacrylalkannin (5-20 mg/kg; p.o.; daily; 14 days) exhibits dose-dependent in vivo anti-hepatocellular carcinoma efficacy, with both 5 mg/kg and 20 mg/kg oral doses significantly reducing tumor growth and proliferation, and the 20 mg/kg dose showing greater potency^[1].
β,β-Dimethylacrylalkannin (60-120 mg/kg; p.o.; daily; 29-57 days) inhibits tumor growth in FGFR1-positive colorectal cancer PDX mice with average tumor weight reductions ranging from 33.6% to 67.8%, and exhibits no notable systemic toxicity^[2].
β,β-Dimethylacrylalkannin (2 mg/kg; i.p.; single dose) combined with colistin (0.2 mg/kg; i.p.; single dose) increases survival to 80% and reduces bacterial organ burdens in mice with systemic Klebsiella pneumoniae infection^[3].
β,β-Dimethylacrylalkannin (10 g/kg; p.o.; single dose) has an oral LD₅₀ greater than 10 g/kg bw in KM mice, with transient mild toxicity signs and no lasting pathological changes in surviving animals^[4].
β,β-Dimethylacrylalkannin (10 g/kg; p.o.; single dose) has an oral MTD greater than 10 g/kg bw in Wistar rats, with only transient mild toxicity signs and no pathological changes observed^[4].
β,β-Dimethylacrylalkannin (10-160 mg/kg/day; p.o.; 6 days per week; 26 weeks) administered orally for 26 weeks at up to 160 mg/kg/day in Wistar rats causes only transient, reversible changes and dose-related renal tubular pigmentation, with a NOAEL of 10 mg/kg/day^[4].